Galanin is a peptide which is widely distributed in the central and peripheral nervous systems. In the pancreas, galanin is present in the sympathetic nerve terminals surrounding the islets of Langerhans and is a major inhibitor of insulin secretion during sympathetic nerve stimulation and certain systemic stresses. Despite these potent effects on insulin secretion, the effect of galanin receptor blockade in type II diabetes has not been investigated because of the lack of suitable galanin receptor blockers. As a prelude to determining the structural requirements of the ligand binding domain of the galanin receptor, the research outlined in this proposal is aimed at elucidating the molecular structure of the galanin receptor, the distribution of galanin receptor subtypes and the determination of the second messenger systems associated with the receptor sub types. The new information gained from achievement of these aims may then be used to determine the molecular requirements for ligand binding and to design galanin receptor antagonists to allow testing of the hypothesis that galanin may play a role in the unfavorable insulin secretion to insulin requirement balance in type II diabetes.